The Lynx Group
Cholangiocarcinoma News

Continuing Progress in Cholangiocarcinoma and Bilary Tract Cancers

March 2021, Vol 2, No 1
Milind M. Javle, MD
Professor
Department of Gastrointestinal Medical Oncology
Division of Cancer Medicine
The University of Texas
M.D. Anderson Cancer Center
Houston, TX
Chair
NCI Task Force: Hepatobiliary Cancers

Dear Colleagues,

It gives me great pleasure to introduce the March issue of CCA News. Once again, we have several recent developments in cholangiocarcinoma (CCA) clinical research, and these have been reviewed by leaders in the field.

At the CCA Summit held during the 2021 ASCO Gastrointestinal Cancers Symposium, Rachna T. Shroff, MD, MS, from the University of Arizona Cancer Center, has provided a detailed overview of the 15 clinical trials and research presented at the meeting that focused on developments in biliary tract cancers and CCA. A succinct summary of her presentation at the meeting is presented in this issue.

These 15 studies include the pivotal phase 2 clinical trial of infigratinib for the treatment of advanced, chemorefractory CCA associated with FGFR2 fusions and gene rearrangements. The results of this trial indicate a new therapeutic opportunity for patients with CCA. We hope that this promising agent receives FDA approval.

The updated results of the clinical trial ClarIDHy indicate an improved overall survival with the IDH1 inhibitor, ivosidenib (Tibsovo), compared with placebo, showing a beneficial effect on patients’ quality of life.

Other novel agents presented at the meeting included silmitasertib, an oral casein kinase 2 inhibitor; zanidatamab, a dual kinase HER2/neu inhibitor; neratinib (Nerlynx); and the novel arginase inhibitor, INCB001158.

This issue also includes several presentations from the 2020 CCA Summit. Abby Siegel, MD, MS, from Merck, provided an insightful and nuanced view of the role of immune checkpoint inhibitors in CCA and biliary tract cancers. Although the efficacy signal of immunotherapy has been somewhat muted, sequencing studies have identified “immunogenic clusters” that need prospective studies. She also noted that the role of chemotherapy as an adjunct to immunotherapy may be context-dependent, with higher responses seen in bladder cancer or lung cancer compared with biliary tract cancers. In the KEYNOTE-158 trial, which involved multiple solid tumors, including biliary tract cancers, a tumor mutational burden (TMB) of ≥10 was associated with a higher response rate than seen in those with low TMB. The median TMB in biliary tract cancers tends to be low.

Flavio Rocha, MD, of Virginia Mason Medical Center, has presented the rationale for the new American Joint Committee on Cancer 8th edition staging system for CCA and the implications for clinical practice.

Neoadjuvant and perioperative strategies are gathering momentum in the management of patients with CCA, as discussed by James Harding, MD, from Memorial Sloan Kettering Cancer Center.

Two recent retrospective studies, one by Hop S. Tran Cao, MD, FACS, from M.D. Anderson Cancer Center, and another from Amit Mahipal, MBBS, MPH, from the Mayo Clinic, have reviewed the National Cancer Database. They suggest that neoadjuvant therapy is being used increasingly for node-positive disease and may result in a survival advantage over upfront surgery.

We look forward to your feedback and contributions in the upcoming issues!

Sincerely,

Milind Javle, MD

Milind Javle, MD
Professor
Department of Gastrointestinal Medical Oncology
Division of Cancer Medicine
The University of Texas
M.D. Anderson Cancer Center
Houston, TX
Chair
NCI Task Force: Hepatobiliary Cancers

Related Items

Mechanisms of Resistance to FGFR Inhibitors
By Jesús Bañales, PhD; Antoine Hollebecque, MD; Milind M. Javle, MD; Angela Lamarca, MD, PhD, MSc
Videos
Drs Javle, Bañales, and Hollebecque discuss the innate and acquired resistance pathways to FGFR inhibitors in cholangiocarcinoma and how these pathways can have important effects on clinical outcomes. They also look ahead to ongoing clinical trials evaluating next-generation FGFR inhibitors that may be able to overcome resistance mechanisms and improve progression-free and overall survival in cholangiocarcinoma.
Molecular Profiling Should Now Be Routine Practice in Patients with CCA
By Milind M. Javle, MD
September/October 2021, Vol 2, No 3
This issue of CCA News features yet another exciting FDA approval for cholangiocarcinoma (CCA), ivosidenib, which was recently approved for CCA with IDH1 mutation. This is the third drug approved for CCA in the past 2 years, highlighting the critical role of molecular profiling in this cancer. Up to 20% of patients with intrahepatic CCA have IDH1 mutation, and the ClarIDHy phase 3 study demonstrated improvement in progression-free survival with ivosidenib versus placebo for chemorefractory disease. The FDA also approved the Oncomine Dx Target Test for IDH1 mutations.
Evolution in Biomarker Testing in CCA
By Jesús Bañales, PhD; Antoine Hollebecque, MD; Milind M. Javle, MD; Angela Lamarca, MD, PhD, MSc
Videos
Using next-generation sequencing to detect FGFR fusion partners and co-mutations to improve efficacy in treating CCA
Incorporating FGFR Inhibitors into the Treatment Paradigm for Cholangiocarcinoma: Current Concepts and Future Directions
By Mitesh J. Borad, MD; Milind M. Javle, MD; Michael Morse, MD, FACP, MHS; Lewis R. Roberts, MB, ChB, PhD
June/July 2021, Vol 2, No 2
On January 15, 2021, experts in the management of patients with cholangiocarcinoma (CCA) convened for a virtual accredited continuing education satellite symposium held during the 2021 annual meeting of the American Society of Clinical Oncology Gastrointestinal Cancers Symposium. The goal was to educate healthcare providers on various aspects of CCA, including epidemiology, current standards of care, unmet clinical needs, the safety and efficacy of fibroblast growth factor receptor (FGFR) inhibitors as second-line therapy, and practical approaches to incorporating FGFR inhibitors into the treatment paradigm for the disease.
Considering Toxicities Associated with Specific and Pan-FGFR Inhibitors
By Jesús Bañales, PhD; Antoine Hollebecque, MD; Milind M. Javle, MD; Angela Lamarca, MD, PhD, MSc
Videos
Drs Javle, Báñales, and Hollebecque describe their thoughts about the use of pan-FGFR inhibitors compared with those that primarily target FGFR2 and the potential of treating CCA with inhibitors of FGFR1, 3, and 4. Moreover, they consider the most common adverse events associated with inhibitors of FGFR2, of which the most difficult to manage are hyperphosphatemia, nail toxicity, eye toxicity, and fatigue. The importance of educating oncologists on how to treat these toxicities is key to maintaining dose intensity of FGFR inhibitors.

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